What is the best course of action for a patient with elevated ferritin, low iron, and possible anemia?

Management of Functional Iron Deficiency with Anemia of Chronic Disease

This 74-year-old patient has functional iron deficiency (FID) in the setting of inflammation, evidenced by low serum iron (10 μmol/L), low-normal transferrin saturation (19%), mild anemia (Hb 112 g/L), and elevated ferritin (533 μg/L), and should receive a trial of intravenous iron therapy.

Understanding the Iron Status Pattern

This patient presents with a classic pattern of functional iron deficiency superimposed on inflammation:

• Low serum iron (10 μmol/L, at lower limit of normal) indicates insufficient iron available for erythropoiesis 1
• Transferrin saturation of 19% falls below the 20% threshold, suggesting iron-restricted erythropoiesis despite adequate stores 1
• Elevated ferritin (533 μg/L) reflects both iron stores and acute phase reaction from underlying inflammation 1
• Mild anemia (Hb 112 g/L, just below 115 g/L lower limit) with normocytic indices (MCV 94 fL) 2

The key distinction here is between functional iron deficiency and an inflammatory iron block. In FID, iron stores exist but cannot be mobilized rapidly enough to support erythropoiesis, whereas in inflammatory block, iron is sequestered and unavailable 1.

Diagnostic Interpretation

Functional iron deficiency is the most likely diagnosis because:

• TSAT <20% indicates inadequate iron delivery to erythroid precursors despite ferritin >100 ng/mL 1
• Ferritin between 100-700 ng/mL with TSAT <20% is the hallmark pattern of FID 1
• The ferritin level of 533 μg/L, while elevated, does not exclude iron deficiency in the presence of inflammation 1

In inflammatory conditions, ferritin up to 100 μg/L may still indicate iron deficiency, and even higher levels don't guarantee adequate functional iron availability 1.

Recommended Treatment Approach

Initiate a therapeutic trial of intravenous iron:

• Administer weekly IV iron 50-125 mg for 8-10 doses as recommended for distinguishing FID from inflammatory block 1
• Monitor hemoglobin response after this trial period 1
• If hemoglobin increases, this confirms functional iron deficiency and justifies continued iron therapy 1
• If no erythropoietic response occurs, an inflammatory block is most likely, and iron should be discontinued until inflammation resolves 1

Why Intravenous Rather Than Oral Iron?

IV iron is preferred in this clinical scenario because:

• The elevated ferritin suggests an underlying inflammatory condition where oral iron absorption may be impaired 1, 2
• IV iron bypasses the hepcidin-mediated block on intestinal iron absorption that occurs with inflammation 2
• Faster and more reliable response compared to oral supplementation in functional iron deficiency 1

Monitoring Parameters

Track the following during iron therapy:

• Hemoglobin levels every 2-4 weeks to assess erythropoietic response 1
• Ferritin and TSAT every 3 months once stable 1
• Avoid chronic maintenance of TSAT >50% or ferritin >800 ng/mL to prevent iron overload 1

The goal is to improve erythropoiesis and hemoglobin, not simply to achieve specific ferritin or TSAT targets 1.

Investigation of Underlying Causes

Simultaneously investigate potential causes:

• Inflammatory conditions: The elevated ferritin (533 μg/L) and white cell parameters suggest possible chronic inflammation 1, 3
• Occult blood loss: Even with elevated ferritin, consider gastrointestinal evaluation in elderly patients with anemia 1, 2
• Chronic kidney disease: Check creatinine and GFR, as CKD commonly causes both anemia and altered iron metabolism 1
• Chronic disease states: Heart failure, inflammatory bowel disease, malignancy, or rheumatologic conditions 1, 2, 3

Critical Pitfalls to Avoid

Do not withhold iron therapy based solely on elevated ferritin. The DRIVE study demonstrated that patients with ferritin 500-1200 ng/mL and TSAT <25% showed significant hemoglobin improvement with IV iron (16±13 vs 11±14 g/L increase, P=0.028) 1. Baseline ferritin was not predictive of iron responsiveness 1.

Do not assume iron overload. Ferritin levels between 300-800 ng/mL are common in dialysis patients without evidence of adverse iron-mediated effects 1. True iron overload typically requires TSAT >80% 1.

Do not use oral iron as first-line therapy in this setting, as the inflammatory milieu impairs absorption and the patient requires a diagnostic trial to distinguish FID from inflammatory block 1, 2.